Causes of Viral Hemorrhagic Fever
Viral hemorrhagic fevers are caused by enveloped RNA viruses from four main families: Arenaviridae (e.g., Lassa virus), Filoviridae (e.g., Ebola virus), Flaviviridae (e.g., yellow fever, dengue), and the order Bunyavirales (e.g., Crimean-Congo hemorrhagic fever, hantaviruses). 1, 2
Viral Families and Specific Pathogens
Arenaviridae
- Lassa virus: The most clinically significant arenavirus, endemic in West Africa with an estimated 300,000-500,000 cases yearly 1
- Junin and Machupo viruses: South American hemorrhagic fever viruses 1
Filoviridae
- Ebola virus: Causes severe VHF with high mortality, responsible for major outbreaks in Africa 3
- Other filoviruses within this family 2
Flaviviridae
- Yellow fever virus: Causes VHF with similar molecular pathogenesis to other VHF agents 4
- Dengue virus: The most common cause of VHF in returning travelers, accounting for 5.2% of febrile cases (15.9% of tropical diseases) 5
Bunyavirales (formerly Bunyaviridae)
- Crimean-Congo hemorrhagic fever virus 1
- Hantaviruses: Cause hemorrhagic fever with renal syndrome 1, 2
- Other bunyaviruses 6
Transmission Routes
Primary Transmission (Zoonotic)
- Rodent reservoirs: Lassa virus is transmitted primarily through contact with excreta of Mastomys natalensis rodents 1
- Vector-borne: Many VHFs involve arthropod vectors in their transmission cycle 2
- Animal contact: Most VHF viruses are zoonotic, causing asymptomatic infections in their natural hosts but potentially lethal disease in humans 6
Secondary Transmission (Human-to-Human)
- Direct contact with infected bodily fluids: Blood, saliva, vomit, stool, or urine 1
- Nosocomial transmission: Well-documented in healthcare facilities, particularly in endemic areas 1
- Note: Secondary transmission is uncommon but represents a significant risk in healthcare settings 1
Epidemiological Context
The geographic distribution is highly variable, with most VHFs being geographically localized to specific endemic regions 7. In returning travelers presenting with fever, malaria remains the most common tropical infection (22.2% of cases), followed by dengue fever (5.2%), and enteric fever (2.3%), while viral hemorrhagic fevers specifically account for only 0.1% of cases 5. However, the severity and outbreak potential of VHFs make them critical to recognize despite their relative rarity in travelers.
Clinical Pitfalls
Do not rely on hemorrhagic manifestations for diagnosis—VHFs initially present as non-specific febrile illnesses with malaise, fever, and muscle aches that may progress to vascular permeability, coagulopathy, and varying degrees of hemorrhage 2, 6. Early laboratory findings typically show leukopenia, thrombocytopenia, and elevated liver enzymes 2.